Real time monitoring of extracellular glutamate release in rat ischemia model treated by nimodipine

Abstract

It is well known that cerebral ischemia is associated with extracellular concentrations of the excitatory amino acids. Real time quantitative measurement of glutamate which is the most abundant excitatory neurotransmitter would be very helpful parameter, in order to evaluate brain injury during or after surgery, as well as validation of the instantaneous effect of drug. In order to define the effect of nimodipine on glutamate release and neuronal cell damage, we monitored real-time extracellular glutamate release and cerebral blood flow (CBF) in an eleven vessel occlusion global ischemia rat model. Changes in glutamate release and CBF were monitored by laser-Doppler flowmetry and amperometric biosensor, respectively. A ten minute 11VO cerebral ischemia was initiated by pulling the snares on the common carotid arteries (CCAs) and the external carotid arteries (ECAs). Nimodipine was infused during the ischemic period (0.025 μg/100gm/min: diluted 20 times by normal saline). The infusion site for nimodipine was located lateral to the probe of cerebral blood flowmeter. Three days after occlusion, histological analysis was performed by Nissel staining, in order to assessment of neuronal cell damage. In comparison with the ischemia and nimodipine group, the maximum changes in glutamate concentration showed statistically significant difference between two groups, resulting in neuronal cell death. It is considered that nimodipine may reduce glutamate release with brain damage during a global ischemic episode in the eleven vessel occlusion rat model. © 2010 Springer-Verlag.